Current brain-computer interface (BCI) systems utilizing the P300 Speller can provide an effective means of communication for locked-in patients if the patients are willing to spend considerable time training to use the system and are willing to accept a fairly slow communication rate. The overarching goal of this research is to transition current P300 Speller BCI systems from research labs to clinical use by increasing system robustness, increasing the communication rate achieved by the patient, and reducing the time required to train the patient to use the system. In the R21 phase of this work, three variations on the standard speller and training paradigm will be evaluated for their potential to achieve these goals: 1) improved real-time stimulus selection via optimal experiment design, 2) channel selection using feature selection techniques, and 3) improved communication rates via the sequential detection of P300 responses. At the completion of the R21 phase, these approaches have the potential to substantively improve communication rates, improve robustness, and increase accuracy in a set of normal subjects. In the R33 phase of this effort, we propose to evaluate the impact of our R21 developments in subjects with disabilities. Specifically, we will begin by assessing the impact of the baseline and improved speller system on subjects with disabilities while operating the system in a clinical environment. Using lessons learned from these subjects in the clinical environment, we will begin testing the baseline and improved system in the home environment. The goal of this phased development and proof of concept effort is to transition the current P300 speller system which operates fairly well in a research environment into a tool that can be used in the home environment by the clinical population for which it was developed. At the successful completion of this R21/R33 effort, an Augmentative and Alternative Communication (AAC) device that can be used in the home by ALS patients with robust and accurate performance will have been demonstrated and should be ready to begin a commercialization phase. While research and laboratory systems exist currently that are based on the P300 speller paradigm, they have not been successfully transitioned to the clinic, or the home. The goal of this effort is to effect that transition from research platform to clinically relevant AAC device prescribable by a clinician. In addition to providing a more powerful research tool in the clinic, ALS subjects would be able to communicate in a robust and accurate fashion in the home.